OBJECTIVES: The long term goal of this project is the elucidation of the mechanisms by which the adrenocortical hormones, glucagon, and the catecholamines control the synthesis of glucose in the liver. The primary objective of the past year has been: to continue the characterization of the changes in hepatic mitochondria brought about by these hormones. PROJECTS OF THE PAST YEAR: Studies were begun that were designed to explore the hypothesis that the hormones acting via cyclic adenylic acid alter the mitochondria by stimulating the phosphorylation or dephosphorylation of mitochondrial proteins. Isolated rat liver cells were incubated with P32. They were then stimulated for a brief period with glucagon. Mitochondria were isolated from the cells and their proteins separated by gel electrophoresis. Autoradiography indicated several P32-labelled proteins. There were no clear-cut changes in labelling of the major compoenets but there were suggested changes in several proteins that were weakly labelled. Studies were made on mitochondria that had their electron transport blocked with antimycin A. These were made to see if electron transport was required for the manifestation of hormonal stimulation. It was found that an ATP-dependent decarboxylation of pyruvate in the presence of valinomycin was accelerated in mitochondria from glucagon-treated rats. Similarly the rate of valinomycin-induced swelling supported by added ATP was also accelerated in mitochondria blocked with antimycin A. The conclusion is that at least some of the effects of glucagon in mitochondria are not dependent on the activity of the respiratory chain. The mitochondrial response to adrenal steriods was studied.